Sodium nitroprusside is a short-acting, parenterally administered vasodilator that is used to treat severe hypertension and cardiac failure. It is also used to treat hypertension in postoperative cardiac surgery patients and to induce hypotension for certain surgical procedures. Toxicity may occur with acute high-dose nitroprusside treatment or with prolonged infusions.

Nitroprusside is rapidly hydrolyzed (half-life, 11 minutes) and releases free cyanide, which normally is converted quickly to thiocyanate by rhodanese enzymes in the liver and blood vessels. Cardiopulmonary bypass-associated free hemoglobin release accelerates the liberation of free cyanide and may increase the risk for cyanide toxicity.

1. Acute cyanide poisoning may occur with short-term high-dose nitroprusside infusions (10 mcg/kg/min) or longer-term administration of lower doses (3-10 mcg/kg/min).
2. Thiocyanate is eliminated by the kidneys and may accumulate in patients with renal insufficiency, especially after prolonged infusions.

The toxic dose depends on renal and hepatic function and the rate of infusion.

1. Clinical cyanide poisoning is uncommon at infusion rates of less than 10 mcg/kg/min, but a dose of 2 mcg/kg/min has been used as a threshold for toxicity. A study in children receiving nitroprusside after cardiac surgery found that a dose of 1.8 mcg/kg/min or greater predicted elevated blood cyanide levels, although not necessarily clinical toxicity. Risk factors for cyanide poisoning include liver disease and therapeutic hypothermia. Sodium thiosulfate may be combined with nitroprusside (10:1 ratio) during high dose infusions (4 mcg/kg/min or higher) to prevent development of cyanide toxicity.
2. Thiocyanate toxicity does not occur with acute brief use in persons with normal renal function but may result from prolonged infusions (eg, >3 mcg/kg/min for ≥48 hours), especially in persons with renal insufficiency (with rates as low as 1 mcg/kg/min).

The most common adverse effect of nitroprusside is hypotension, which often is accompanied by reflex tachycardia. Peripheral and cerebral hypoperfusion can lead to lactic acidosis and altered mental status.

1. Cyanide poisoning may be accompanied by headache, dizziness, nausea, vomiting, anxiety, agitation, delirium, psychosis, tachypnea, tachycardia, hypotension, loss of consciousness, seizures, and metabolic acidosis. ECG may reveal ischemic patterns. Increased mixed venous blood oxygen levels may be observed.
2. Thiocyanate accumulation causes somnolence, confusion, delirium, tremor, and hyperreflexia. Seizures and coma rarely occur with severe toxicity.
3. Dose-related methemoglobinemia rarely occurs and is usually mild.

Lactic acidosis, altered mental status, or seizures during short-term high-dose nitroprusside infusion should suggest cyanide poisoning, whereas confusion or delirium developing gradually after several days of continuous use should suggest thiocyanate poisoning.

1. Specific levels. Whole blood cyanide levels may be obtained but are not usually available rapidly enough to guide treatment. In addition, levels may not accurately reflect toxicity because of simultaneous production of methemoglobin, which binds some of the cyanide. Levels higher than 0.5 mg/L are considered elevated, and levels higher than 1 mg/L usually produce lactic acidosis. Thiocyanate levels higher than 50-100 mg/L may cause delirium and somnolence.
2. Other useful laboratory studies include electrolytes, glucose, BUN, creatinine, serum lactate, ECG, arterial blood gases and measured arterial and venous oxygen saturation (see “Cyanide,”), and methemoglobin level (with use of a co-oximeter).

1. Emergency and supportive measures
   1. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen.
   2. For hypotension, stop the infusion immediately and administer IV fluids and vasopressors if necessary.
2. Specific drugs and antidotes. If cyanide poisoning is suspected, administer hydroxocobalamin, or sodium thiosulfate if hydroxocobalamin is unavailable. Avoid the use of sodium nitrite as it may aggravate hypotension. A constant intravenous infusion of hydroxocobalamin (25 mg/h) is sometimes co-administered with high-dose nitroprusside as prophylaxis against cyanide toxicity.
3. Decontamination. These procedures are not relevant because the drug is administered only parenterally.
4. Enhanced elimination. Nitroprusside and cyanide are both metabolized rapidly, so there is no need to consider enhanced elimination for them. Hemodialysis may accelerate thiocyanate elimination and is especially useful in patients with renal failure.